Chiral borane reagents

ABSTRACT

Chiral borane reagents and their organosilicon derivatives are disclosed.

BACKGROUND OF THE INVENTION

The government has rights in this invention under Grant No.NIH-5-RO1-GM33039-02 from the National Institute of Health and underIPA-0010.

This invention relates to novel chiral borane reagents, their method ofpreparation, and their use in performing asymmetric reactions includinghydroboration, ketone reduction, aldol condensation, nucleophiliccarbonyl addition, and the Diels-Alder reaction.

Double asymmetric synthesis concerns the interaction of two homochiralreactants, a substrate and a reagent. Evidence has accumulated to showthat the ratio of the diastereomeric products resulting through aprocess of double asymmetric snythesis can be approximated to be (a×b)or (a÷b) where a and b represent the diastereofacial selectivities(D.S.) of the two chiral reactants, respectively. When one of the chiralreactants is replaced by an achiral model reactant in this reaction, theresulting product ratio, a or b, is referred to as the diastereofacialselectivity of the chiral reactant which is not replaced. Thus, a and brepresent the extent (and directionality) of a single asymmetricinduction. If the two chiral reactants act in concert to enhance thestereoselectivity of the double asymmetric reaction to a×b, then theyconstitute a matched pair. If not, they are called a mismatched pair andthe selectivity is reduced to a÷b. A corollary of this multiplicativityrule which is now established bears a signigicant consequence: A chiralreagent with a large D.S. which can be, and has been devised, is capableof augmenting or overriding the D.S. of a preselected substrate to suchan extent that even in a mismatched case, the stereoselectivity of a(double symmetric) reaction is brought to a synthetically meaningfulvalue (for example, 20:1). In order to achieve this controlled highselection, the D.S. of a reagent must be in the order of 100:1 with asubstrate with a D.S. of 5:1 or less. This demand has been met forseveral major organic reactions such as the aldol reaction. TheDiels-Alder reaction, and the epoxidation of allylic alcohols, and thestrategy of reagent controlled organic synthesis (as opposed to thetraditional substrate controlled organic synthesis) has beensuccessfully applied to the synthesis of stereochemically complexnatural products. The syntheses of 6-deoxyerythronolide B and manyothers described in Masamune et al., Angew Chem. Int. Ed. Engl., 1985,24, pg. 1, amply illustrate this strategy.

In designing chiral boron reagents which are capable of mediatingseveral organic reactions, it is appropriate to start withhydroboration, a reaction that plays an important role in achieving manyorganic transformations. Thus, hydroboration followed by oxidation,amination, protonolysis, and many other reactions constitute a means ofproviding alcohols, amines, alkanes (from alkenes), and others normallywith high efficiency, and regio- and stereoselection. An asymmetricversion of this hydroboration began in 1961 with the discovery of thechiral reagent, diisopinocampheylborane (Ipc₂ BH), Brown et al., J. Am.Chem. Soc., 1961, 83, 486, and thus far this compound and three otherreagents, dilongifolylborane, (Lgf₂ BH), Jadhav et al., J. Org. Chem.,1981, 46, 2988, limonylborane (LimBH), Jadhav et al., Heterocycles,1982, 18, 169, monoisopinocampheylborane (IpcBH₂), Brown et al.,Synthesis, 1978. 146, have been examined to find the degree of singleasymmetric induction. Since the mutual interactions between a prochiralolefin and a chiral reagent effect asymmetric induction, each of theabove reagents with four types of olefins has been evaluated: Type I,2-methyl-1-alkenes; Type II, Z-disubstituted; Type III, E-disubstituted;and Type IV, trisubstituted alkenes. ##STR1## Both olefins and reagents,each having different steric demands, will induce energy differences dueto interaction (mainly steric) in their corresponding diastereomerictransition states, the degree of which will be reflected on theefficiency of asymmetric hydroboration. At the same time, however, largesteric interactions may also result in major decreases in reactivity.The steric demand of the olefins increases from Type I to Type IV, whilethe reagents Ipc₂ BH, Lgf₂ BH, LimBH, and IpcBH₂ are in decreasing orderof the demand. Thus, Ipc₂ BH, the reagent of largest steric demands, ismost favorable for asymmetric hydroboration of Type II olefins withrelatively low steric demands. Type II olefins are not handledsatisfactorily by any of the other reagents (ee 0-30%). Ipc₂ BH does notreact with either Type III or IV. Both Lgf₂ BH and LimBH handle threemajor classes of alkenes, Types II, III, and IV, but with only good butnot excellent asymmetric induction (roughly in the neighborhood of 50%ee). IpcBH₂, the reagent of lowest steric demands, is capable ofhydroborating alkanes of very large steric demands (Type IV) sometimeswith high % ee (53-88%). 1-Phenylcyclopentene is an exceptional case(100% ee). However, IpcBH₂ fails with Types I and II olefins (1.5-24%ee). Many dialkylboranes resulting from the reaction of IpcBH₂ with TypeIV olefins are highly crystalline and can be recrystallized to achieveproducts of essentially 100% optical purity, Brown et al., J. Am. Chem.Soc., 1984, 106, 1797. However, this procedure owes it success to theefficient resolution technique and cannot be applied to either expensiveolefins or chiral olefins which must be used in many important chemicaltransformations.

Accordingly, it would be desirable to provide reagents having a veryhigh diastereofacial selectivity which permits the stereospecificproduction of organic products in a wide variety of organic reactions.##STR2## wherein R is selected from the group including primary andsecondary alkyls and trimethylsilyl.

The chiral borolanes of this invention are capable of converting achiralsubstrates with enantiomeric excesses averaging about 98%. Theeffectiveness of these reagents render them useful in performingasymmetric reactions including hydroboration, ketone reduction, aldolcondensation, nucleophilic carbonyl addition, and the Diels-Alderreaction.

DESCRIPTION OF SPECIFIC EMBODIMENTS

The compounds of this invention are prepared by a process represented byscheme 1 set forth below (for compounds 2-5, see beginning of examples).##STR3##

For the case where R is methyl in formulas 1a and 1b, (a) is Cl₂ BNEt₂,ether THF, -78° C.; (b) HCl/ether, MeOH, pentane, 0° C.; (c) Me₂ NCH₂CH₂ OH, pentane, room temperature; (d) (S)-prolinol, pentane, 0° C.; (e)(S)-valinol, pentane, 0° C.; (f) LiAlH₄, MeOH, ether, 0° C.; (g) Mel,ether, room temperature; (h) (R,R)-12, Mel, ether, room temperature; (i)HOCH₂ CH₂ OH, 2 or 6N NaOH/MeOH, THF, 30% H₂ O₂, 40°-50° C.

For the case where R is ethyl in compounds 1a and 1b, the entireprocedure is the same as above except for Step C where Me₂ NCH₂ CH₂ OHis replaced by N-piperidino-2-ethanol ##STR4##

For the case where R is isopropyl (1a' and 1b'), Scheme II is used fortheir preparations. ##STR5## (j) NaH/Me₂ SO; (k) BH₃.THF and then MeOH;(l) N-pyrrolidino-2-ethanol, pentane, -20°--78° C.; (b), (d), (e), (f),(g) are the same as above.

Compounds 1c and 1d are prepared according to Scheme III and outlinedbelow. ##STR6## This procedure is general for all 1c and 1d whereR=methyl, ethyl, and isopropyl.

In hydroboration, olefins are converted to alcohols in a multi-stepprocedure (h,i in Scheme I). The borolanes of this invention are addedto a solution of the olefin followed by the addition of iodomethane. Theresultant composition is heated to a temperature between about 20° and25° C. for a time of between about 10 and about 20 hours. The solvent isremoved and the residue then is dissolved in a suitable solvent such astetrahydrofuran. Subsequently, a glycol such as ethylene glycol and amethanolic base such as sodium hydroxide together with hydrogen peroxideis added to the solution which is then heated at a temperature betweenabout 40° and 50° C. for about 1 to 5 hours. The alcohol product isrecovered by continuous extraction.

In ketone reduction, a ketone is dissolved in a suitable solvent such aspentane and is admixed with the borolane of this invention. A mixture of30% hydrogen peroxide and 3N NaOH is added to the resultant compositionand the corresponding alcohol is extracted by a suitable organicsolvent.

In an aldol condensation, a methyl or ethyl ketone is mixed with aB-trifluoromethanesulfoxyborolane (1c and 1d) and diisopropylethylamineand to the resulting boron enolate solution is added an aldehyde at -78°C. After stirring at the same temperature, the resulting composition istreated with 30% hydrogen peroxide at pH 7 and extracted with ether. Theorganic extracts contain the corresponding aldol product.

In nucleophic carbonyl addition, the reaction is effected as outlined inScheme IV. ##STR7##

In the Diels-Alder reaction, a dienophile such as maleic anhydride isreacted with a diene such as cyclopentadiene to produce an adduct in thepresence of a B-methoxyborolane [(R,R)-8 or (S,S)-8] of this invention.The reaction generally is conducted at a temperature between about -78°to -40° C. for a period of time between about 15 minutes and 1 hour andthe adduct is recovered by 1) dilution with ether, washing with a sodiumbicarbonate solution, and concentration of the organic layer.

The following examples illustrate the present invention and are notintended to limit the same: In the Table on page 23, compounds 2, 3, 4and 5 refer to the following compounds: ##STR8##

EXAMPLE I ##STR9## 1-(N,N-diethylamino)-2,5-dimethylborolane 7

Dibromoethane (3.0 mL, 0.035 mol) was added to a mechanically stirredsuspension of Mg turnings (78 g, 3.21 mol) in THF (160 mL). After 30min. most of the THF was removed via cannula and fresh THF (270 mL) wasadded. Then a solution of 2,5-dibromohexane (299 g, 1.24 mol) in THF(650 mL) was added at a rate that maintained the internal temperature at30°-34° C. The resulting mixture was stirred overnight, filtered throughglass wool and diluted with THF to a volume of 2 L. Hydrolysis of analiquot and titration for total base showed the concentration of thissolution to be 0.39M (63% yield, typically 60-65%). The Grignardsolution was added to a cooled, magnetically stirred solution ofN,N-diethylaminodichloroborane (124 g, 0.80 mol) in ether (1.0 L) at arate that allowed maintenance of an internal temperature of -70° to -65°C. The resulting suspension was allowed to warm to 20° C. overnight. Thesolids were allowed to settle and the supernatant was removed viacannula. The solids were washed with pentane (four times) and thecombined supernatants were concentrated by fractional distillation. Theresidue was vacuum transferred to a cold (dry ice-acetone) receiver byheating the residue to 120° C. at 0.1 torr. Distillation under reducedpressure gave the diethylaminoborolane 7 as a mixture of isomers (72.8g, 0.44 mol) in 56% yield. On a small scale yields up to 70% wereobtained.

bp 79°-82° C. (15 torr); ¹ H NMR δ0.83(3H, d, J=7.7 Hz), 0.93(3H, d,J=7.2 Hz), 1.04(6H, d of t, J=1.0, 7.2 Hz), 1.05-1.80(6H, m),3.0-3.2(4H, m); ¹³ C NMR δ15.4, 15.6, 22.8, 33.7, 34.2, 42.6; ¹¹ B NMRδ50.

EXAMPLE II ##STR10## Cis- and trans-1-methoxy-2,5-dimethylborolane 8

A solution of ethereal HCl (234 mL, 0.80 mol) was slowly added to acooled, mechanically stirred solution of methanol (41.3 mL, 1.02 mol)and diethylaminoborolane 7 (131 g, 0.78 mol) in pentane (1.3 L). Theinternal temperature was maintained between 5°-10° C. A whiteprecipitate formed during the addtion and the resulting suspension wasstirred at 20° C. for 12 h. The solution was filtered, the precipitatewashed with pentane and the solvent removed from the filtrate bydistillation at atomospheric pressure through a 50 cm Vigreaux column.The residue was distilled under reduced pressure to give methoxyborolane8 as a colorless oil (85 g, 67 mol, 86% yield, cis:trans ratio 47:53).

bp 49°-52° C. (33 mm). For other physical data see characterization ofpure isomers below.

EXAMPLE III ##STR11##(R,S)-1-(2-N,N-dimethylaminoethoxy)-2,5-dimethylborolane 9 andtransmethoxyborolane (±) 8

N,N-dimethylethanolamine (11.5 mL, 114 mmol, 45 mol %) was added to amagnetically stirred solution of cis- and trans-methoxyborolanes 8 (32.0g, 0.254 mmol) in pentane (220 mL) at room temperature. After 2 h thesolution was vacuum transferred to a receiver cooled in dry ice-acetone.The transfer was completed by reducing the pressure to 0.1 torr andheating the reaction flask to 70°-80° C. The white crystalline residuewas essentially pure cis complex 9 (21.0 g, 114 mmol, 100%, cis:transratio >98:2 by ¹ H NMR). Recrystallization from pentane gave pure 9. Thevacuum transferred material was treated with a second portion ofdimethylethanolamine (2.1 ml, 21 mmol, 8 mol %). Vacuum transfer asabove gave a solid residue (4.2 g, 23 mmol, 109% cis:trans ratio 1:2).The vacuum transferred material was concentrated by distillation atatmospheric pressure. The residue was distilled at reduced pressure togive trans-methoxyborolane (±)-8 (12.9 g, 103 mmol, 86%, cis:trans ratio2:98).

Data for complex 9

mp 59°-60° C.; ¹ NMR δ 0.55(2H, m), 0.82(6H, d, J=7.3 Hz), 1.1-1.6(4H,m), 2.49(6H, s), 2.85(2H, t, J=7 Hz); ¹³ C NMR δ 17.0, 23.4, 34.9, 44.6,59.1, 59.5; ¹¹ B NMR δ 12.8; mass spectrum, m/z (relative intensity),183 (7), 182(2.4), 140(29), 126(17), 72(44), 58(100).

Data for trans-methoxyborolane (±) 8

bp 51°-54° C. (34 torr); ¹ H NMR δ 0.95(6H, br s), 1.05-1.2(2H, m),1.8-2.0(4H, m), 3.80(3H, s); ¹³ C NMR δ 14.0, 24.5, 33.5, 55.1; ¹¹ B NMRδ 57.

EXAMPLE IV ##STR12## Prolinol complex 10 and valinol complex 11

(S)-(+)-prolinol (4.66 g, 46.1 mmol, 45 mol %) in ether (5 ml) was addeddropwise to a magnetically stirred solution of trans-borolane 8 (12.9 g,102 mmol) in pentane (100 mL) at 0° C. A white precipitate formed duringthe addition. The suspension was stirred 30 min at 0° C. and 1.5 h at20° C. The volatile materials were vacuum transferred to a receivercooled in dry ince-acetone. The transfer was completed by reducing thepressure to 0.1 torr and raising the temperature to 70°-80° C. The whitecrystalline residue was nearly pure prolinol complex 10 (9.14 g, 46.8mmol, 102%). Crystallization from CH₂ Cl₂ gave the pure complex.

mp 225°-226° C.; ¹ H NMR δ 0.50-0.70(2H, m), 0.89(6H, d, J=7.2 Hz),1.7-1. 85(4H, m), 2.0-2.2(2H, m), 2.85-3.2(2H, m), 3.56(1H, dd, J=3.2,9.2 Hz), 3.60-3.75(1H, m), 3.91(1H, dd, J=6.2, 9.1 Hz), 4.1-4.25(1H, brs); ¹³ C NMR δ 18.0, 26.0, 27.2, 31.2, 36.6, 48.6, 61.5, 67.4; ¹¹ B NMRδ 11; mass spectrum, m/z (relative intensity), 195(10.4), 194(6.6),152(73), 139(64), 138(58), 84(50), 70(100); [α]_(D) ²¹ +23.2 (c1.28CHCl₃).

The volatile material was treated with a second portion of prolinol(1.02 g, 10.2 mmol, 10 mol %). Vacuum transfer as above gave a 1:1mixture of prolinol complexes (2.19 g, 11.2 mmol, 110%). The volatilematerial was treated with (S)-(+)-valinol (4.78 g, 46.3 mmol, 45 mol %)in ether (5 ml). Removal of the volatiles in vacuo (0.1 torr, 80° C.)gave nearly pure valinol complex 11 (8.77 g, 44.6 mmol, 96%).Recrystallization from CH₂ Cl₂ -pentane gave the pure complex.

mp 151°-154° C.; ¹ H NMR δ 0.40-0.60(2H, m), 0.88(6H, d, J=7.2 Mz),96(3H, d, J=7.2 Hz), 1.16(3H, d, J=7.2 Hz), 1.6-1.8(4H, m), 2.8-3.0(1H,m), 3.56(1H, dd, J=9.9 Hz), overlaps 3.45-3.65(2H, br s), 4.00(1H, dd,J=7.9 Hz); ¹³ C NMR δ 19.0, 20.1, 27.0, 31.0, 36.0, 60.9, 66.4; ¹¹ B NMRδ 12; mass spectrum, m/z (relative intensity) 197(0.7), 170(9.7),170(9.7), 154(54), 72(100); exact mass calculated for C₁₁ H₂₄ BNO, m/z197.1951, Found 197.1950; [α]_(D) ²¹ -3.33° (c 1.17, CHCl₃).

EXAMPLE V ##STR13## Synthesis of (R,R)-methoxyborolane 8 fromaminoalcohol complex 10

A solution of ethereal HCl (15.4 ml, 18.8 mmol) was added dropwise to amagnetically stirred solution of methanol (0.95 ml, 23 mmol) andprolinol complex 10 (3.50 g, 17.9 mmol) in pentane (50 mL) at 0° C.After 6 h the solution was filtered. The filtrate was concentrated bydistillation through a Vigreaux column at atmospheric pressure and theresidue was distilled at reduced pressure (60°-61° C., 61-63 mm Hg) togive (R,R)-8 (1.83 g, 81% yield). In a similar manner valinol complex 11was converted to (S,S)-8 in 70% yield.

EXAMPLE VI ##STR14## Synthesis of (S,S)- and(R,R)-dihydro-2,5-dimethylboratacyclopentane ethereate 12

An ethereal solution of LiAlH₄ (59.8 mL, 14.5 mmol) was slowly added toa magnetically stirred solution of the desired methoxyborolane 8 (1.83g, 14.5 mmol) in ether (5 mL) at 0° C. A gelatinous precipitate formedduring the addition. The solution was warmed to 20° C. and stirred to 1h. The solution was cooled in an ice bath and methanol (1.06 mL, 26.2mmol) was added dropwise. After 2 h at 20° C., the solution wasfiltered. Removal of the solvent in vacuo (20° C., 0.1 torr) gaveborohydride 12 as the monoethereate (2.02 g, 78% yield).

¹ H NMR (C₆ D₆) δ 0.98(6H, t, J=7.2 Mz), 1.26(2H, m), 1.42(6H, d, J=6.8Mz), 1.55(2H, m), 2.28(4H, m), 3.11(2H, dq, J=6.9, 10.1 Hz), 3.18(2H,dq, J=7.2, 10.1 Hz); ¹³ C NMR (C₆ D₆) δ 14.4, 22.3, 24.1, 38.9, 66.3; ¹¹B NMR (C₆ D₆) δ-11.6(t, J=70 Hz).

EXAMPLE VII ##STR15## Typical procedure for asymmetric hydroboration ofolefins

Borohydride R,R-12 (3.6 mL, 1.8 mmol, 0.50 solution in ether) was addedto a solution of 2-methyl-2-butene (1.59 mL, 1.5 mmol) in ether (2 mL)at 4° C. Then iodomethane (0.224 mL, 3.6 mmol) was added. The solutionwas stirred at 22° C. for 15 h. The solvent was removed in vacuo (50torr) and the residue was dissolved in THF (1.3 mL). Ethylene glycol(0.2 mL, 3.6 mmol, degassed), methanolic NaOH (2.7 mL, 10.8 mmol,degassed) and 30% H₂ O₂ (0.9 mL, 9 mmol) were added at 4° C. Thesolution was heated to 40°-50° C. for 2 h. Continuous extraction withpentane (25 mL) gave a solution containing primarily 3-methyl-2-butanol.Continuous extraction with ether (20 mL) gave a solution of2,5-hexanediol. The residue (ca. 1.5 mL) was diluted with pentane (2.5ml) and decane (0.100 mL) was added as an internal standard for GCanalysis. A portion (0.4 mL) of the pentane solution was acetylated withacetic anhydride (0.5 mL), pyridine (0.5 mL) and 4-dimethylaminopyridine(DMAP) (3 mg). After the usual workup GC analysis showed that theoverall yields of 2-acetoxy-3-methylbutane and 2,5-diacetoxyhexane were90 and 26%, respectively. Chromatography of the remaining pentanesolution (ether/pentane, 1:4), concentration at atmospheric pressure andbulb to bulb distillation (320 torr, 80°-100° C. T_(b)) gave3-methyl-2-butanol (105 mg). The MTPA ester of this alcohol was preparedas follows: A solution of the alcohol (10 mg), DMAP (2 mg), pyridine (1.ml) and (R)-MTPA chloride (0.030 mL) in CH₂ Cl₂ (1 ml) was stirred at20° C. for 12 h. After the usual workup HPLC analysis of this oil (0.3%ether/hexane, 2 mL/min) showed two peaks in a ratio of 97.1 (t_(R) 34.5min) to 2.9 (t_(R) 32.3 min).

The ether solution from continuous extraction was dried (MgSO₄),evaporated and distilled (bulb-to-bulb, 30 torr, 120°-130° C. T_(b)) togive 2,5-hexanediol (161 mg, 76%). The bis-MTPA ester was prepared asabove. HPLC analysis (7% ether/hexane, 2 mL/min) showed 95.7% of theMTPA ester of the R,R diol (t_(R) 18.4 min), 4.3% of the bis-MTPA esterof the R,S diol (t_(R) 22.1 min) and <0.3% of the bis MTPA ester of theS,S diol (t_(R) 25.7 min). Thus the ee used to correct the opticalpurity of the butanol was 95.7.

    TABLE I      Asymmetric Hydroboration with Achiral Olefins with 1a, 2, 3, 4, and 5     With 1a of 96.5% or 97.5% ee.sup.a  % ee of 15 corrected for the     enantiomeric reaction % ee purity of each chiral borane used   olefin     time, h.  % yield  of 15  (Ipc).sub.2 BH(2) (Lgf).sub.2 BH(3) LimBH(4)     IpcBH.sub.2 (5) entry olefin type (temp.) alcohol 15 of 15.sup.b     [α].sub.D.sup.21 of 15.sup.c obtained 1a (config.).sup.d (config.).     sup.d (config.).sup.d (config.).sup.d                     1      ##STR16##      .sup.e I      1     ##STR17##      85 .sup.f+0.25° (c 1.18,CHCl.sub.3)  .sup.g 1.4  1.5 (-  S) 32     (.sub.--R).sup.h 2      ##STR18##      .sup.i II 36 (4° C.)      2     ##STR19##      75 .sup.j+13.3° (c 0.63,CH.sub.3 OH)      .sup.k95.2     ##STR20##      99.1 (.sub.--R) 78 (.sub.--R) 55.0 (.sub.--R) 24 (- S) 3      ##STR21##      .sup.e II      6.5     ##STR22##      83 .sup.l+8.86° (c 0.93,C.sub.2 H.sub.5 OH)      .sup.m96.4     ##STR23##      94.1 (.sub.--R) 71 (.sub.--R) 4      ##STR24##      .sup.i  III 12 (-20° C.)48 (4° C.)      6     ##STR25##      71 .sup.j+13.4° (c 0.71,CH.sub.3 OH)      .sup.k97.0     ##STR26##      14 (.sub.--R).sup.h 25 (- S) 58.6 (.sub.--R) 73 (- S) 5      ##STR27##      .sup.e III 10      ##STR28##      83 .sup.l+8.83° (c 1.05,C.sub.2 H.sub.5 OH)      .sup.m96.0     ##STR29##         75 (- S) 6      ##STR30##      .sup.e IV 15      ##STR31##      90 .sup.n+5.04° (c 1.13,C.sub.2 H.sub.5 OH)      .sup.k94.2     ##STR32##      15 (.sub.--R).sup.h 70 (.sub.--R) 66.5 (.sub.--R) 53 (- S) 7      ##STR33##      .sup.e IV      9.5     ##STR34##      89 .sup.o+46.6° (c, 1.13,CH.sub.3 OH)      .sup.m97.0     ##STR35##      24 (- S,- S) 63 (.sub.--R,.sub.--R) 45.0 (.sub.--R,.sub.--R) 66     (- S,- S) 8      ##STR36##      .sup.i IV 96      ##STR37##      .sup.p60 (69) .sup.q+37.8° (c 1.16,CH.sub.3 OH)  .sup.k93.2      ##STR38##         77 (- S,- S)      9     ##STR39##      .sup.e IV 12      ##STR40##      97 .sup.r-10.6 (c 1.36,CCl.sub.4)      .sup.k95.8     ##STR41##       52 (.sub.--R)     .sup.a Reaction in ethyl ether using 1.2 equiv of (R,R)12 and 2,4 equiv o     CH.sub.3 I at room temperature (21-23° C.) unless otherwise noted.     .sup.b Determined by GC analysis after acetylation [ (CH.sub.3 CO).sub.2    4(CH.sub.3).sub.2 NC.sub.5 H.sub.4 N].     .sup.c All optical rotations were measured at the alcohol stage except     entry 9 (acetate).     .sup.d Data from Brown's reports (ref 7 and the following: Brown, H. C.;     Ayyangar, N. R.; Zweifel, G. J. Am. Chem. Soc. 1964, 86, 1071). All     numbers are corrected for the optical purity of the starting material.     .sup.e (R,R)12 of 96.5% ee was used for hydroboration.     .sup.f R alcohol [α].sub.D.sup.28 -2.95° (c 60.521,     CHCl.sub.3): Tsuda, K.; Kishida, Y.; Hayatsu, R. J. Am. Chem. Soc. 1960,     82, 3396.     .sup.g Based on .sup.1 H NMR of the MTPA ester.     .sup.h (+)(Ipc).sub.2 BH derived from (-)α-pinene was used.     .sup.i (R,R)12 of 97.5% ee was used.     .sup.j Commercially available S alcohol (81.6% ee HPLC analysis of MTPA     ester, Aldrich Chemical Co.) [α].sub.D.sup.21 +12.0° (c 1.12     CH.sub.3 OH).     .sup.k HPLC analysis of the derived MTPA esters: Dale, J. A.; Dull, D. L.     Mosher, H. S. J. Org. Chem. 1969, 34, 2543.     .sup.l S alcohol [α].sub.D.sup.20 +8.0 (c 0.6, C.sub.2 H.sub.5 OH):     Davies, J.; Jones, J. B. J. Am. Chem. Soc. 1979, 101, 5405.     .sup.m HPLC analysis of the Pirkle's carbamates: Pirkle, W. H.; Hoekstra,     M. S. J. Org. Chem. 1974, 39, 3904.     .sup.n S alcohol [α].sub.D.sup.25 +5.34° (c 5.0, C.sub.2     H.sub.5 OH): Pickard, R. H.; Kenyon, J. J. Chem. Soc. 1913, 103, 1923.     .sup.o 1S,2S alcohol [α].sub.D.sup.25 +43.9° (c 1.00,     CH.sub.3 OH): Partridge, J. J.; Chadha, N. K.; Uskokovic, M. R. J. Am.     Chem. Soc. 1973, 95, 532.     .sup.p Yield in parenthesis is based on consumed starting material.     .sup.q 1S,2S alcohol [α].sub.D.sup.20 +42.9° (c 1, CH.sub.3     OH): Backstrom, R.; Sjoberg, B. Ark. Kemi 1967, 26, 549.     .sup.r (S)1-Acetoxy-1-cyclohexylethane of 32 ± 6% ee shows     [α].sub.D.sup.25 -1.6° (c 1.1, CCl.sub.4): This (-)isomer wa     erroneously recorded as having an R configuration (personal communication     from Professor Meyers): Meyers, A. I.; Ford, M. E. J. Org. Chem. 1976, 41     1735.

EXAMPLE VIII Analysis of optical purity of complexes 10, 11,methoxyborolane 8 and borohydride 12

The optical purities of the above compounds were determined as follows:A solution of the appropriate borolane (0.1 mmol) in THF (2 mL) wasoxidized by the addition of ethylene glycol (0.012 mL), 2N methanolicNaOH (0.3 mL, 0.6 mmol) and 30% H₂ O₂ (0.05 mL) followed by heating to40°-50° C. for 2 h. The solution was cooled, diluted with ether (5 mL)and saturated with anhydrous K₂ CO₃. The solution was filtered and thefiltrate dried over K₂ CO₃. Filtration and removal of the solvents invacuo (20° C., 0.1 torr) gave crude 2,5-hexanediol. Treatment with(R)-MTPA chloride (3 equiv) as above gave the bis-MTPA diesters whichwere analyzed by HPLC. When samples were analyzed at each stage, theeffective enantiomeric excesses so determined were in agreement within±1%.

Our use of the term enantiomeric excess is not, strictly speaking,proper because our calculations include a correction for the presence ofthe cis isomer. The cis isomer is treated as though it were a 1/1mixture of the (R,R) and (S,S) compounds. Thus an HPLC analysis showingthe presence of 95% (R,R), 4% (R,S) and 1% (S,S) diesters provides aneffective ee of (95+2)-(1=2) or 94% ee.

EXAMPLE IX Determination of Absolute Configurations of complexes 9, 10,11

A solution of prolinol complex 10 (779 mg, 4.0 mmol) in THF (20 mL) wasoxidized as above with ethylene glycol (0.44 mL, 7.9 mmol), 2Mmethanolic sodium hydroxide (12 mL, 24 mmol) and 30% H₂ O₂ (2 mL, 20mmol). Ether (50 mL) was added and the solution was washed with brine(2×10 mL). The aqueous phase was extracted with ether (2×10 mL). Thecombined organic layers were dried (K₂ CO₃) and evaporated.Chromatography (ethyl acetate) of the residue afforded(R,R)-2,5-dihydroxyhexane (356 mg, 75% yield). The idol was acetylatedwith acetic anhdride (1.5 mL) and DMAP (30 mg) at 20° C. for 12 h.Standard workup followed by chromatography (ethylacetate/hexane, 1:9)gave (R,R)-2,5-diacetoxyhexane (482 mg, 80% yield). Bulb-to-bulbdistillation gave pure diacetate.

bp 90°-90° C. (4 torr); [α]_(D) ²¹ +3.00 (c 8.32, CHCl₃); ¹ H NMR δ 1.18(6H, d, J=6.2 Hz), 1.55(4H, m), 2.00(6H, s), 4.86(2H, m); ¹³ C NMR δ19.8, 21.1, 31.5, 70.4, 170.4.

A solution of this diacetate (349 mg, 1.73 mmol) in THF (5 mL) was addedto a suspension of LiAlH₄ (131 mg, 3.45 mmol) in THF (10 mL) at 4° C.and stirred for 1 h. Ether (15 mL) was added followed by 1M aq NaOH (0.5mL) and the insoluble material was removed by filtration. Evaporationgave (R,R)-2,5-dihydroxyhexane (217 mg, 100%). Bulb-to-bulb distillationafforded pure diol. bp 90°-100° C. (4 torr); mp 51°-53° C.; ¹ H NMR δ1.18(6H, d, J=6.1 Hz), 1.54(4H, m) 2.06(2H, s), 3.84(2H, m); ¹³ C NMR δ23.6, 36.0, 68.2; [α]_(D) ²¹ -31.9° (c 7.38, CHCl₃). Serck-Hannsen, K.;Stallberg-Stenhangen, S.; Stenhangen, E. Ark. Kemi, 1953,5,203: found[α]_(D).sup. 23 -35.6 (c 8.29, CHCl₃). The bis-MTPA ester of this diolwas prepared as above and shown to be a 92% R,R 4% S,S mixture ofdiesters.

Oxidation and acetylation of the valinol complex gave(S,S)-2,5-diacetoxyhexame (57% yield) identical with the (R,R)-diacetateexcept for rotation. [α]_(D) ²¹ -3.27 (c 7.98, CHCl₃). Reduction withLAH gave (S,S)-2,5-dihydroxyhexane (100% yield) identical with(R,R)-diol except for rotation.

[α]_(D) ²¹ +34.2 (c 6.82, CHCl₃. Serck-Hanssen et al.: found [α] 25+35.1(c 9.49, CHCl₃). The bis MTPA ester was 1% R,R, 3% R,S and 96% S,S.

Oxidation and acetylation of the cis complex gave(R,S)-2,3-diacetoxyhexane (70% yield). bp 80°-90° C. (4 torr); ¹ H NMR δ1.21(6H, d, J=6.2 Hz), 1.56(4H, m), 2.03(6H, s), 4.87(2H, m); ¹³ C NMR δ19.8, 21.1, 31.7, 70.5, 170.4; [α]_(D) ²¹ -0.027 (c 7.53, CHCl₃).Reduction with LAH gave (R,S)-2,5-dihydroxyhexane. bp 90°-100° C. (4torr); ¹ H NMR δ 1.18(6H, d, J=6.1 Hz), 1.55 (4H, m), 2.03(2H, s),3.84(2H, m); ¹³ C NMR δ 25.2, 34.8, 67.6; [α]_(D) ²¹ 0° (c 8.06, CHCl₃).The bis-MTPA ester was 4% R,R, 92% R,S and 4% S,S.

EXAMPLE X

Ketone reduction with (R,R)-2,5-dimethylborolane

Treatment of alkyl ketones with (R,R)-2,5-dimethylborolane provided thecorresponding alcohols with excellent enantioselection. The degrees ofasymmetric induction (% e.e.) are 100 >95 and 76 for tertiery, secondaryand primary alkyl groups, respectively, as exemplified in table II.##STR42##

                  TABLE II                                                        ______________________________________                                                                          absolute                                    R         temp (°C.)                                                                       yield    % ee configuration                               ______________________________________                                                  r.t.      80       99.8  -S                                          ##STR43##                                                                              -20       70       95.5  -S                                         n-C.sub.6 H.sub.13                                                                      -30       72       85.0  -S                                         ______________________________________                                    

EXAMPLE XI The Aldol Reaction

Aldol reactions using the triflate (trifluoromethylsulfonate) (1c),derived from (R,R)-10 under the conditions specified below proceededstereoselectively.

EXAMPLES ##STR44##

Note that Examples A and B are two types of enantio-selectivetransformations which are almost impossible with other aldol methods.

EXAMPLE XII Carbonyl Addition Reaction

A typical example is shown below schematically. ##STR45##

I claim:
 1. A compound of the formula:wherein R is a primary orsecondary alkyl or trimethylsilyl group.
 2. The compound of claim 1having the structure of 1a wherein R is methyl.
 3. The compound of claim1 having the structure of 1b wherein R is methyl.
 4. The compound ofclaim 1 having the structure of 1a wherein R is ethyl.
 5. The compoundof claim 1 having the structure of 1b wherein R is ethyl.
 6. Thecompound of claim 1 having the structure of 1a wherein R is isopropyl.7. The compound of claim 1 having the structure of 1b wherein R isisopropyl.
 8. The compound of claim 1 having the structure of 1a whereinR is trimethylsilyl.
 9. The compound of claim 1 having the structure of1b wherein R is trimethylsilyl.
 10. The compound of claim 1 having thestructure of 1c wherein R is methyl.
 11. The compound of claim 1 havingthe structure of 1d wherein R is methyl.
 12. The compound of claim 1having the structure of 1d wherein R is ethyl. PG,33
 13. The compound ofclaim 1 having the structure of 1d wherein R is ethyl.
 14. The compoundof claim 1 having the structure of 1c wherein R is isopropyl.
 15. Thecompound of claim 1 having the structure of 1d wherein R is isopropyl.16. The compound of claim 1 having the structure of 1c wherein R istrimethylsilyl.
 17. The compound of claim 1 having the structure of 1dwherein R is trimethylsilyl.